Project Summary The goal of this research is to use gene and protein expression patterns to develop point of care diagnostic tool that can serve as a guiding tool to optimize debridement for non-healing venous leg ulcers (VLUs). Thus, it will identify objective and reliable biomarkers that will guide wound practitioners to make informed decision when wound edge debridement is adequate. We have shown that biopsies obtained from the non- healing edges of VLUs before/after debridement have distinct morphologies and distinguishable gene and protein expression patterns. Cells generated from pre-debridement edge biopsies exhibit a non-healing phenotype as evidenced by loss of migration and loss of ability to respond to growth factors, suggesting a loss of healing potential whereas cells genrated from post-debridement biopsy are migratiory and responsive to growth factors. Some clinical data show a positive response in VLUs wound size reduction following wound bed debridemet. However, wound bed debridement is not always considered standard of care for VLUs. Therefore we aim to compare effectivnes of two therapeutic approaches: standard of care (i.e. compression therapy) and wound bed debridement coupled to standard of care. The intervention arm will consit of two subgroups, a) one that utilizes gene/protein expression-guidaded debridement protocol, and b) uses standard clinical debridement protocol for VLUs. We hypothesize that gene/protein expression patterns can be utilized to guide wound edge debridement in VLUs and further that such biomarker-guided debridement will improve healing outcome in patients suffering from chronic non-healing VLUs. Also, based on genomic profiles we plan to develop specific PCR- and immunostain-based methods to serve as a simplified diagnostic test to guide the extent of debridment. Thus, we will conduct a randomized clinical trial to test if gene expression patterns can be utilized as a guiding tool for the debridement extent and to test the effect of wound edge debridement on healing progression (Aim 1) and develop PCR- and/or immunostain-based complementary assessment method and validate it for guiding surgical debridement (Aim 2). We will proceed with genomic profiling and compare gene expression patterns of specimens obtained before and after debridement. Next, expression patterns will be correlated with healing outcomes comparing patients with wounds that progressed to healing with those that did not at 4 weeks post intervention. The proposed study is the first step in incorporating gene/protein wound signatures as a clinical tool. Successful completion of this study will provide objective biological markers to guide wound edge debridement in patients suffering from VLUs. Incorporation of molecular tools into armory of intervention will result in a paradigm shift that will alter the course of healing, decrease morbidity, mortality, and lower associated treatment costs.